{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T16:32:58Z","timestamp":1792773178369,"version":"4.5.0"},"reference-count":73,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:00Z","timestamp":1792713600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P35541"],"award-info":[{"award-number":["P35541"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P31074"],"award-info":[{"award-number":["P31074"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Small"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Bacterial survival in acidic environments depends on urea channels like UreI, which neutralize protons after importing urea and hydrolyzing it to ammonia and carbon dioxide. While pH\u2010dependent gating was attributed to periplasmic histidines, the role of cytoplasmic residues remained unexplored. Using yeast complementation assays, in vitro permeability measurements, systematic sequence analysis, and molecular dynamics simulations, we identify a conserved cytoplasmic glutamic acid residue (E136 in\n                    <jats:italic>Streptococcus salivarius<\/jats:italic>\n                    , E135 in\n                    <jats:italic>Helicobacter hepaticus<\/jats:italic>\n                    , E159 in\n                    <jats:italic>Helicobacter pylori<\/jats:italic>\n                    ) as a pH sensor in UreI channels. Protonation of this residue disrupts its interaction with a conserved partner (R20 in\n                    <jats:italic>S. salivarius<\/jats:italic>\n                    and\n                    <jats:italic>H. hepaticus<\/jats:italic>\n                    , T170 in\n                    <jats:italic>H. pylori<\/jats:italic>\n                    ), increasing cytoplasmic\u2010loop flexibility and enhancing conformational sampling of a conserved aromatic triad in the selectivity filter, thereby facilitating urea permeation. Mutagenesis across\n                    <jats:italic>S. salivarius<\/jats:italic>\n                    ,\n                    <jats:italic>H. pylori<\/jats:italic>\n                    , and\n                    <jats:italic>H. hepaticus<\/jats:italic>\n                    confirms the residue\u00b4s indispensable and conserved role, revealing a Gram\u2010type\u2010specific gating mechanism: Gram\u2010positive bacteria rely solely on this glutamic acid sensor, while Gram\u2010negative pathogens employ a dual\u2010sensor model integrating both cytoplasmic glutamic acid and periplasmic histidines. By overturning the paradigm of exclusive periplasmic pH sensing, this work reveals a conserved yet adaptable mechanism for bacterial acid resistance, offering a new molecular target for precision antimicrobial development.\n                  <\/jats:p>","DOI":"10.1002\/smll.76130","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T14:27:36Z","timestamp":1792765656000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Cytoplasmic pH Sensor Redefines Gating in Bacterial Urea Channels and Acid Resistance"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2362-091X","authenticated-orcid":false,"given":"Anna","family":"Stoib","sequence":"first","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar","family":"Shojaei","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xenia","family":"Fischer","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4400-5412","authenticated-orcid":false,"given":"Sandra","family":"Posch","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9900-4663","authenticated-orcid":false,"given":"Gianluca","family":"Parisse","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences University of L'Aquila  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-4106","authenticated-orcid":false,"given":"Mario","family":"Frezzini","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, Computer Science and Mathematics University of L'Aquila  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5108-859X","authenticated-orcid":false,"given":"Tobias","family":"Putz","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8294-1960","authenticated-orcid":false,"given":"Christine","family":"Siligan","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6572-5606","authenticated-orcid":false,"given":"Nikolaus","family":"Goessweiner\u2010Mohr","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2731-6286","authenticated-orcid":false,"given":"Daniele","family":"Narzi","sequence":"additional","affiliation":[{"name":"Department of Physical and Chemical Sciences University of L'Aquila  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5328-1745","authenticated-orcid":false,"given":"Andreas","family":"Horner","sequence":"additional","affiliation":[{"name":"Institute of Biophysics Johannes Kepler University Linz  Linz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,23]]},"reference":[{"issue":"6","key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/nrc2857","article-title":"Helicobacter pylori: Gastric Cancer and Beyond","volume":"10","author":"Polk D. 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